Human CD4- CD8- αβ+ T cells express a functional T cell receptor and can be activated by superantigens

Abstract

The CD4 and CD8 molecules play an important role in the stimulation of T cells and in the process of thymic education. Most mature T cells express the αβ TCR and either CD4 or CD8; however, there is a small population of αβ+ TCR T cells that lack both CD4 and CD8. Little is known of the biology of the CD4- CD8- (double-negative) αβ+ TCR T cells or the nature of the Ag to which they may respond. These cells not only represent a novel population of T cells but also provide useful biologic tools to study the roles that CD4 and CD8 play in T cell activation. In this study we have addressed two questions. Firstly, whether CD4- CD8- αβ+ TCR T cells have functionally active TCR and, secondly, whether CD4 or CD8 is required for the activation of T cells by bacterial enterotoxins. Six double-negative αβ+ TCR T cell clones, propagated from two healthy donors, were challenged with a panel of nine bacterial enterotoxins. The Vα and Vβ usage of their TCR was determined by polymerase chain reaction. All of the CD4- CD8- clones proliferated in response to at least one of the enterotoxins, in a Vβ-specific manner. The proliferative response of the CD4- CD8- αβ+ TCR T cell clones was similar in magnitude to that exhibited by CD4+ T cell clones of known Vβ expression. These data clearly show that the CD4 and CD8 molecules are not required for the activation of untransformed human T cells by bacterial enterotoxins. Furthermore, these results indicate that CD4- CD8- αβ+ TCR T cells, normally present in all individuals, are not functionally silent, because they can be stimulated via their TCR. Their physiologic role, like that of γδT cells, remains to be elucidated.